Previous researches suggested microRNA-140-3p (miR-140-3p) and miR-155-5p as cancer promotor in chordoma. We aimed to investigate the mechanisms of these two miRNAs in chordoma cells. Patient-derived chordoma cell lines were established in vitro. Expressions of miR-140-3p or miR-155-5p were measured by quantitative real-time polymerase chain reaction and their functions were inhibited by antagomir treatment. Malignancy of chordoma cells was assessed by cell viability, proliferation, apoptosis, colony formation and transwell invasion assays as well as western blot evaluating epithelial-to-mesenchymal transition. Sensitivity of chordoma cells was assessed by cell viability and apoptosis assays. Protein level of phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI3K)- protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway were assessed by western blot. Interaction of miR-140-3p and miR-155-5p with the 3' untranslated region of PTEN mRNA was verified by luciferase reporter assay. BpV was used to inhibit PTEN activity. The expressions of miR-140-3p and miR-155-5p were enhanced in chordoma cells and inhibited by treatment of antagomirs. Inhibition of miR-140-3p or miR-155-5p significantly reduced the malignancy of patient-derived chordoma cells and activation of PI3K-Akt-mTOR signaling, while significantly increasing the sensitivity to doxorubicin, paclitaxel or cisplatin treatment and PTEN protein level. PTEN was verified as a direct target of miR-140-3p and miR-155-5p and its inhibition by bpV treatment largely abrogated the chemotherapy sensitizing effect of anti-miR-140-3p or anti-miR-155-5p on chordoma cells. Collectively, inhibition of miR-140-3p or miR-155-5p significantly reduced the malignancy of chordoma cells and increased their sensitivity to chemotherapy by releasing PTEN expression.
[1]Jilin Univ, China Japan Union Hosp, Dept Orthoped, Xiantai St 126, Changchun 130033, Jilin, Peoples R China.
[2]Jilin Univ, China Japan Union Hosp, Dept Anesthesiol, Changchun 130033, Jilin, Peoples R China.
[3]Changchun Obstet Gynecol Hosp, Dept Nursing, Changchun 130042, Jilin, Peoples R China.
(8.0+极速模式)